Baseline neutrophil-to-lymphocyte ratio predicts drug retention of IL-6 inhibitors and JAK inhibitors in RA: the ANSWER cohort study

OBJECTIVE: This study aimed to compare drug retention rates according to the baseline neutrophil-to-lymphocyte ratio (NLR) in patients with RA initiating biologic/targeted synthetic DMARDs (b/tsDMARDs). METHODS: Data were obtained from 774 treatment courses with moderate to high disease activity at the initiation of b/tsDMARD therapy from the Kansai Multicentre ANSWER cohort. Patients were categorized into NLRlow group and NLRhigh group based on the median NLR value of 3.30. A multivariate Cox proportional hazards model, adjusted for potential confounders, was used to estimate hazard ratios (HRs) for drug retention over 2 years. RESULTS: Patients in the NLRhigh group exhibited significantly higher baseline Clinical Disease Activity Index (CDAI) scores (P = 0.004) and more frequent glucocorticoid use (P < 0.001) than those in the NLRlow group. In the NLRlow group, drug retention rates did not significantly differ among tumour necrosis factor inhibitors (TNFi), anti-IL-6 receptor antibodies (aIL-6R), cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4-Ig) and Janus kinase inhibitors (JAKi). In contrast, within the NLRhigh group, treatment with aIL-6R and JAKi was associated with significantly higher retention rates compared with TNFi (HR = 0.53, 95% CI: 0.32-0.88; HR = 0.36, 95% CI: 0.20-0.64, respectively). At 12 months, CDAI scores did not significantly differ among the four treatment groups in either NLR group. CONCLUSION: In patients with elevated baseline NLR values, aIL-6R and JAKi may offer superior drug retention compared with TNFi when initiating b/tsDMARD therapy.